This multidisciplinary program project will coordinate biochemical, physiological, pharmacological, and clinical approaches in order to understand the role of humoral factors in circulatory homeostasis. "The Physiology and Pathophysiology of Vasoactive Humoral Systems" is the central theme of this program project. Major research emphasis will be placed on joint investigation of a) the kallikrein-kinin, prostaglandin, and adenosine systems in the kidney, and the roles played by these systems in renal function, renal hemodynamics, and renin secretion; b) the kallikrein-kinin system in the salivary and sweat glands, the pancreas, and the gastrointestinal tract, and the roles played by this system in each of the organs, and c) the kallikrein-kinin system effects on metabolic substrate uptake and utilization in isolated adipose cells. The Program Project will integrate the research activities and funding of the Hypertension Research Laboratory at Henry Ford Hospital with those of other investigators having closely related interests. Four Core Units (Administrative, Immunoassay, Biochemistry, and Biostatistics) will support and facilitate the scientific efforts of seven project investigators. Special expertise will be centralized in the core units so that money, space and equipment can be used most efficiently. In addition, use of the core facilities will remove the burden of day-to-day administrative and methodological concerns from project investigators, so that participants will be free to expend their time and energy directly on experimental or clinical projects. The scientists of the Hypertension Research Laboratory already have created an environment of excitement that is conducive to high quality research. We propose to incorporate as a Program Project to achieve a better integration in which our continuing collaboration and sharing of ideas and expertise will accelerate the acquisition of new knowledge on the role of humoral factors in circulatory homeostasis.